The semi-synthetic production of a desacetoxycephalosporin antibiotic by ring expansion of a penicillin starting material has been important since the advent of the invention by Morin and Jackson (U.S. Pat. No. 3,275,626) who describe and claim a process for converting a penicillin sulfoxide ester to an ester of a desacetoxycephalosporin. Several and varied improvements have been made upon this Morin-Jackson process (see, for example, British Pat. No. 1,204,972; British Pat. No. 1,204,394; and U.S. Pat. No. 3,591,585).
The mechanism which is postulated in U.S. Pat. No. 3,275,626 for the ring expansion of the penicillin sulfoxide ester to an ester of a desacetoxycephalosporin is by scission of the S-C.sub.2 bond to form a sulfenic acid intermediate. This mechanism has now been established conclusively (see R. D. G. Cooper, J.A.C.S., 92, (1970) pp. 5010-5011). The sulfenic acid intermediate is then ring-closed to produce the ester of a desacetoxycephalosporin.
It has now been found to be possible to effect a ring expansion of a penicillin sulfoxide ester to produce therefrom a desacetoxycephalosporin sulfoxide ester. In accordance with known techniques, such sulfoxide can be readily converted to an active cephalosporin antibiotic by reduction of the sulfoxide group and cleavage of the ester function to produce the free acid or a pharmaceutically acceptable salt thereof.